Identification of putative miR direct targets by microarray data
Overview
Introduction

This pipeline infers putative direct gene targets of miRs based on miR and gene expression profiles across multiple samples.

Summary

This pipeline use a relevance network approach to infer putative miR:mRNA regulatory connections. All miR:mRNA pairs that have correlations < -0.3 and have predicted interactions in three sequence prediction databases (Miranda, Pictar, Targetscan) define the final network.

Results
Significant miR:gene pairs

Figure 1.  Get High-res Image All miR hubs with their strong anti-correlated genes and predicted interactions in three sequence prediction databases.

Table 1.  Get Full Table List of miR:gene pairs with corr < -0.30 and predicted interactions in three sequence prediction databases.

miR gene Corr prediction databases miranda pictar targetscan total
hsa-mir-29b MLLT11 -0.504 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b TDG -0.469 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b DNMT3A -0.467 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a TDG -0.464 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a MYBL2 -0.460 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b VASH2 -0.456 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b MFAP2 -0.450 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a DNMT3B -0.441 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b BLMH -0.433 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a MLLT11 -0.424 miranda,pictar,targetscan 1 1 1 3
miR connections

Table 2.  Get Full Table All miR hubs with their associated genes in the putative direct target network.

Mir Number.of.Genes Genes
hsa-mir-29b 24 BLMH, COL2A1, COL4A2, DGKD, DNMT3A, DNMT3B, EIF4E2, ENTPD7, FAM130A1, GPX7, HIF3A, JARID1B, JARID2, MFAP2, MLLT11, MYBL2, SPAST, TDG, TRIM37, TUBB, TUBB2A, TUBB2B, VASH2,FSTL1
hsa-mir-29a 21 BLMH, CALM3, COL2A1, COL4A2, DNMT3A, DNMT3B, ENTPD7, FAM130A1, GPX7, JARID2, MFAP2, MLLT11, MYBL2, RIT1, SPAST, TDG, TRIM37, TUBB, TUBB2B, VASH2,EIF4E2
hsa-mir-29c 14 COL2A1, COL4A2, DNMT3A, EIF4E2, GPX7, JARID2, MFAP2, MLLT11, SPAST, TDG, TUBB, TUBB2B, VASH2,FSTL1
hsa-mir-30c 3 MMD, ZEB2,ZNF706
hsa-mir-183 2 MEF2C,DUSP10
hsa-mir-9 2 LMNA,KCTD12
hsa-mir-142-3p 2 HMGA2,CCNT2
hsa-mir-182 2 MMD,MEF2C
hsa-mir-26a 1 EZH2
hsa-mir-26b 1 TMEM2
Gene connections

Table 3.  Get Full Table All gene hubs with their associated miRs in the putative direct target network.

Gene Number.of.Mirs Mirs
TDG 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
GPX7 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
TUBB 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
VASH2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
SPAST 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
DNMT3A 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
EIF4E2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
MFAP2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
JARID2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
COL4A2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
Methods & Data
Input

This section should list the files that were used as input.

  • Level 3 miR expression file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MergeDataFilesPipeline/OV-TP/22229639/GDAC_MergeDataFiles_12185920/OV-TP.mirna__h_mirna_8x15kv2__unc_edu__Level_3__unc_DWD_Batch_adjusted__data.data.txt

  • Level 3 gene expression file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MergeDataFilesPipeline/OV-TP/22230063/GDAC_MergeDataFiles_20410428/OV-TP.transcriptome__ht_hg_u133a__broad_mit_edu__Level_3__gene_rma__data.data.txt

  • miR:gene predicted interactions file = /xchip/cga/reference/miR_predictions/human_interactions.predicted.v2.txt

  • Miranda = microrna.org Aug 2010 release, Microcosm version 5

  • Pictar = version 1

  • Targetscan = release 5.2

Pearson corelation

Pairwise Pearson correlations coefficients between all miR:gene pairs are first computed. All genes that have correlation values less than the user-defined threshold (-0.3) with a particular miR and have been predicted as targets of that miR in three sequence based prediction databases: Miranda[1][2] Pictar[3][4], TargetScan [5][6][7] are identified as putative direct targets of that miR. We infer a direct target miR:gene network which comprises all such putative direct associations.

  • threshold = -0.3

References
[1] Betel D, Wilson M, Gabow A, Marks DS, Sander C, microRNA target predictions: The microRNA.org resource: targets and expression, Nucleic Acids Res 36:D149-53 (2008)
[2] John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS, miRanda: Human MicroRNA targets., PLoS Biol 3(7):e264 (2005)
[3] Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, Piedade ID, Gunsalus KC, Stoffel M, Rajewsky N, Combinatorial microRNA target predictions, Nature Genetics 37:495-500 (2005)
[4] Chen K, Rajewsky N, Natural selection on human microRNA binding sites inferred from SNP data., Nat Genet 38:1452-1456 (2006)
[5] Lewis BP, Burge CB, Bartel DP, Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets., Cell 120(120):15-20 (2005)
[6] Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP, MicroRNA Targeting Specificity in Mammals: Determinants beyond Seed Pairing., Molecular Cell 27:91-105 (2007)
[7] Friedman RC, Farh KK, Burge CB, Bartel DP, Most Mammalian mRNAs Are Conserved Targets of MicroRNAs., Genome Research 19:92-105 (2009)
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